DNA methylation derived systemic inflammation indices are associated with head and neck cancer development and survival

Srikant Ambatipudi*, Ryan Langdon, Rebecca C. Richmond, Matthew Suderman, Devin C. Koestler, Karl T. Kelsey, Nabila Kazmi, Christopher Penfold, Karen M. Ho, Wendy McArdle, Susan M. Ring, Miranda Pring, Tim Waterboer, Michael Pawlita, Tom R. Gaunt, George Davey Smith, Steve Thomas, Andy R. Ness, Caroline L. Relton

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)
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Abstract

Objectives: Head and neck squamous cell carcinoma (HNSCC) is often associated with chronic systemic inflammation (SI). In the present study, we assessed if DNA methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC and overall survival (OS).

Materials and Methods: We used two peripheral blood DNA methylation datasets: an HNSCC case-control dataset (n= 183) and an HNSCC survival dataset (n= 407) to estimate mdSI indices. We then performed multivariate regressions to test the association between mdSI indices, HNSCC development and OS.

Results: Multivariate logistic regression revealed that elevated mdNLR was associated with increased odds of being an HNSCC case (OR=3.25, 95%CI = 2.14-5.34, P = 4x10-7) while the converse was observed for mdLMR (OR=0.88, 95%CI = 0.81-0.90, P = 2x10-3). In the HNSCC survival dataset, HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 x 10-5) and a lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox regression in the HNSCC survival dataset revealed that lower mdLMR (HR= 1.96, 95%CI =1.30-2.95, P = 0.0013) but not lower mdNLR (HR= 0.68, 95%CI = 0.46-1.00, P = 0.0501) was associated with increased risk of death.

Conclusion: Our results indicate that mdSI estimated by DNA methylation data is associated with the presence of HNSCC and overall survival. The mdSI indices may be used as a valuable research tool to reliably estimate SI in the absence of cell-based estimates. Rigorous validation of our findings in large prospective studies is warranted in the future.
Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalOral Oncology
Volume85
Early online date5 Sep 2018
DOIs
Publication statusPublished - 1 Oct 2018

Structured keywords

  • ICEP

Keywords

  • DNA methylation
  • Head and neck cancer
  • Lymphocyte-to-monocyte ratio
  • mdNLR
  • Neutrophil-to-lymphocyte ratio
  • Overall survival
  • Systemic inflammation

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  • Projects

    IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

    Gaunt, L. F. & Davey Smith, G.

    1/04/1831/03/23

    Project: Research

    Rework of IEU 2 Relton Programme

    Relton, C. L.

    1/04/1831/03/23

    Project: Research

    NIHR BRC Nutrition

    Ness, A. R.

    1/04/1731/03/22

    Project: Research, Parent

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